The bactericidal mechanism of carbon monoxide (CO) and the feasibility of CO-releasing molecules as anti-infective drugs were summarized by consulting scientific literature, combined with our own research work. Anaerobic bacteria are usually tolerant to high concentration of CO, and some can even grow with CO as sole carbon or energy source, but most pathogenic bacteria are sensitive to CO. In view of the difficulty of gaseous CO in controlling the applying dose and the action site, CO release molecules were synthesized. CO release molecules not only have higher bactericidal activities against common pathogenic bacteria than gaseous CO, but also have the ability to kill antibiotics-resistant bacteria and destroy their biofilms. CO mainly binds with heme-Fe²⁺ in cells, interrupting the electron transfer of respiration chains, which would result in the generation of reactive oxygen species. CO can also disturb intracellular ion balance, which further triggers free radical reactions. Due to its diverse acting targets, uneasy to induce drug resistance, and synergistic effect with other antibiotics, CO is expected to be the next generation of anti-infection drugs.

To introduce peptidoglycan recycling and the β-lactams resistance mechanisms of bacteria, so that some help would be supplied to corresponding scientific workers and university teachers. By searching literatures, combined with our own studies, the bactericidal mechanisms of β-lactams and the resistance mechanisms of bacteria to β-lactams were summarized. The bactericidal activity of β-lactams is resulted from the inhibition of cell wall biosynthesis through combination with penicillin binding proteins such as transpeptidase destruction of peptidoglycan balances between biosynthesis and hydrolysis. The drug resistance of bacteria is resulted from the induction of β-lactamase, expression of out-pumping proteins, increase of outmembrane permeability, and modification of antibiotic target proteins. The proteins related to peptidoglycan recycling, such as transpeptidase and glycosyltransferase, would be potential targets for screening new β-lactams. The proteins related to β-lactams resistance, such as β-lactamase, would be potential targets for screening adjuvant drugs of β-lactams.

Drug Delivery Systems ; methods ; Drug Design ; Drug Evaluation, Preclinical ; methods ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Microarray Analysis ; RNA ; chemistry ; metabolism ; RNA Interference ; RNA, Small Interfering ; chemistry ; genetics ; Surface Plasmon Resonance

Visceral leishmaniasis (VL) is a parasitic disease ,which is still endemic in western China .An earthquake struck south-western China on May 12th ,2008 ,which affected Longnan City of Gansu Province considerably .The objective of this survey is to determine the effect of the Wenchuan earthquake on the Kala-azar epidemic in Longnan City .In this study ,VL cases were collected from 2005 to 2013 and diagnosed on positive test for anti-rK39IgG antibodies by the Kala-azar Detect rK39 dip-stick (InBios ,USA) .The incidence rates were calculated among various counties of Longnan City with SPSS 19 .0 soft-ware .The epidemiological characteristics of the disease were analyzed before and after the Wenchuan earthquake .From 2005 to 2013 ,there were 825 VL cases in Longnan City ,with an annual incidence of 3 .36/100 000 and a significantly higher incidence in males than that in females (P＜ 0 .001) .All age groups were affected .During this period ,there was an obvious upward trend from 2005 to 2008 ,and a distinct downward tendency since 2010 .The incidences of VL between 2008 and 2010 were sig-nificantly different with that in other years (P＜0 .01) .Results revealed that VL was widespread in Longnan City ,which was likely exacerbated by the earthquake in 2008 .Earthquake created diverse natural environment and social circumstances ,w hich may contribute to the spread of the VL epidemic .Together ,our data strongly suggest that the epidemic of VL should be close-ly monitored after earthquake .

AIMSTo screen for the predominant bacteria strains distributed in clean rooms and to analyze their phylogenetic relationships.

METHODS AND RESULTSThe bacteria distributed in air, surfaces and personnel in clean rooms were routinely monitored using agar plates. Five isolates frequently isolated from the clean rooms of an aseptic pharmaceutical production workshop were selected based on their colony and cell morphology characteristics. Their physiological and biochemical properties, as well as partial 16S rDNA sequences, were analyzed. Results showed that all the five isolates belong to Gram positive bacteria, of which three were Staphylococcus, one Microbacterium and one Bacillus species. Sensitivity tests for these bacteria isolates to 3 disinfectants showed that isolate F03 was obtuse, and had low susceptivity to UV irradiation, while isolates F02, F01 and F04 were not sensitive to phenol treatment. Isolates F04, F01 and F05 were resistant to chlorhexidine gluconate.

CONCLUSIONBacteria widely distributed in clean rooms are mainly a group of Gram positive strains, showing high resistance to selected disinfectants.

SIGNIFICANCE AND IMPACT OF THE STUDYClean rooms are essential in aseptic pharmaceutical and food production. Screening bacteria isolates and identifying them is part of good manufacturing practices, and will aid in finding a more effective disinfection method.

Bacteria ; classification ; genetics ; isolation & purification ; Drug Industry ; Environment, Controlled ; Industrial Microbiology

Objective To study the clinical feature,treatment,and prognosis of the cytomegalovirus (CMV)pneumonia patients treated with immunosuppressor against kidney disease.Mlethod The patients received immunosuppressor against kidney disease in The First Affiliated Hospital of Sun Yat-sen University from June 1999 to December 2006.CMV antigen of leucocyte in the peripheral blood and/or bronchoalveolar lavage fluid of these patients were detected with immunocytochemical methods,and 21 patients were found suffering from CMV pneumonia.The 21 patients were introvenously injected with ganciclovir 5～10 mg/(kg?d),and the immunosuppressive agent treatment suspended.Their clinical feature and prognosis were retrospectively analyzed. Results The 21 patients received corticosteroids before CMV pneumonia contracted,of them,13 patients had been intensively treated with Methyllprednisolone with mean total dose(3.2?0.6)g.Of them,15 had been treated with cyclophosphamide with mean total dose(3.8?1.3)g.The median time from the beginning of using immunosuppressor to the onset of CMV pneumonia was 25(13～92)days.All patients had fever,cough, shortness of breath and X-ray showed interstitial pneumonia,of them,19 patients developed hypoxemia,and 11 patients' CMV antigen was positive in the leucocyte from bronchial lavage fluid.The result showed 9 patients survived and 12 died.The average duration of treatment with ganciclovir was(26.2?6.3)days. CMV pneumonia is a serious complication in patients who were treated with immunosuppressor against kidney disease.The mortality is high.Ganciclovir is a medicine of choice to treat CMV pneumonia.

Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis C, Chronic ; complications ; drug therapy ; psychology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Mental Disorders ; complications ; Middle Aged

OBJECTIVETo investigate the applied anatomy of the superficial peroneal artery perforator flap and report the clinical results of repairing the soft tissue defects with free perforator flaps.

METHODS15 fresh cadavers were injected with a modified lead oxide-gelatin mixture for three-dimensional visualization reconstruction using a 16-slice spiral computed tomography scanner and specialized software (Materiaise's interactive medical image control system, MIMICS). The origin, course and distribution of the superficial peroneal artery perforator in the anterolateral leg region were observed. Clinically 6 cases with hand defects and 6 cases with feet defects were treated with free superficial peroneal artery perforator flap transplantation. The defect size ranged from 3.0 cm x 4.5 cm to 5.0 cm x 11.0 cm.

RESULTSThe diameter of the superficial peroneal artery is (1.2 +/- 0.3) mm at its origin from the anterior tibial artery 5 cm below the fibula head. It is (5.6 +/- 1.8) cm in length. This artery is truly anastomosed with other perforators to form the chain of superficial peroneal nerve accessory artery. The superficial peroneal artery perforators [outer diameter (0.7 +/- 0.2) mm] with a vein are in the anterolateral leg region, supplying the skin in proximal-middle region. All the 12 cases were treated successfully. The clinical results were satisfactory after 3-12 months of following-up.

CONCLUSIONSThe superficial peroneal artery perforator flap has constantly, reliable blood supply, and good texture. It is a good option for repairing soft-tissue defect with free transfer.

Cadaver ; Fibula ; Foot ; Foot Injuries ; surgery ; Free Tissue Flaps ; blood supply ; innervation ; transplantation ; Hand Injuries ; surgery ; Humans ; Leg ; Perforator Flap ; blood supply ; innervation ; transplantation ; Peroneal Nerve ; Soft Tissue Injuries ; surgery ; Tibial Arteries

OBJECTIVETo compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mandatory ventilation (CMV) on the myocardial function of rabbits with inhalation injury.

METHODSSteam inhalation injury model was reproduced in 16 New Zealand albino rabbits. They were randomly divided into CMV group (n = 8) and HFOV group (n = 8) by drawing lots, and they received ventilation in metered volume and HFOV treatment respectively. Heart blood was drawn from rabbits before they were sacrificed 4 hours after treatment to determine the plasma activity of lactate dehydrogenase 1 (LDH1) and creatine phosphorylated kinase (CPK-MB). Myocardial tissue from left ventricle was harvested and homogenized to determine the concentration of TNF-α and IL-8, the activity of caspase-1, and the activity of myosin-light-chain kinase (MLCK) and the ATPase of myosin light chain (MLC-ATPase) by enzyme-linked immunosorbent assay, spectrophotometry, and the nuclide liquid scintillation technique respectively. Part of the myocardial tissue sample was examined pathologically. Data were processed with analysis of variance.

RESULTS(1) The activities of LDH1 and CPK-MB in plasma were obviously higher in CMV group than in HFOV group [(643 ± 108), (342 ± 48) U vs. (233 ± 92), (186 ± 36) U, with F value respectively 10.326 and 9.846, P values all below 0.01]. (2) The contents of TNF-α, IL-8 and the activity of caspase-1 in myocardial tissue homogenate were obviously higher in CMV group than in HFOV group [(181 ± 35), (89 ± 19) pg/g, and (0.56 ± 0.27) g/g protein vs. (94 ± 21), (43 ± 11) pg/g, and (0.24 ± 0.12) g/g protein, with F value respectively 8.239, 7.826, 5.716, P values all below 0.01]. (3) The activities of MLC-ATPase and MLCK were lower in CMV group than in HFOV group [(0.24 ± 0.12) µmol×mg(-1)×min(-1), (3.3 ± 1.1) mmol×mg(-1)×min(-1) vs. (0.48 ± 0.16) µmol×mg(-1)×min(-1), (7.7 ± 1.7) mmol×mg(-1)×min(-1), with F value respectively 4.125, 4.766, P values all below 0.01]. (4) No obvious necrosis, degeneration or inflammatory cell infiltration was observed in myocardial tissue of rabbits in 2 groups under light microscope; but the myocardial fiber was slightly swollen, and it was less marked in the HFOV group.

CONCLUSIONSThe influence of HFOV on myocardial myosin phosphorylation system of rabbits with inhalation injury is less than that of CMV.

Animals ; Burns, Inhalation ; metabolism ; physiopathology ; therapy ; High-Frequency Ventilation ; Myocardium ; metabolism ; Myosin-Light-Chain Kinase ; metabolism ; Rabbits ; Respiration, Artificial

OBJECTIVETo investigate the effects of high frequency oscillatory ventilation (HFOV) and its combination with administration of pulmonary surfactant (PS) on inflammatory response of lung tissue in rabbits with inhalation injury.

METHODSSevere steam inhalation injury models were reproduced in 24 New Zealand albino rabbits. They were divided into control group (n = 8), HFOV group (n = 8), and HFOV + PS group (n = 8) according to the random number table, and they received ventilation in metered volume, HFOV, and HFOV + PS treatment respectively. Lung tissue samples of rabbits were collected at 3.5 h after treatment for pathological inspection and pulmonary injury score, assay of the activity of myeloperoxidase (MPO) and cysteinyl aspartate-specific protease 1 (caspase-1), and the determination of the contents of TNF-alpha, IL-18, IL-10, IL-13 and their mRNA expression.

RESULTSPathological change in different degree of rabbit lung tissue in each group were observed, and they were most obvious in the control group, and least in the HFOV + PS group. The lung tissue injury scores of control group, HFOV group, and HFOV + PS group was 3.71 +/- 0.43, 2.87 +/- 0.26, and 2.08 +/- 0.28 respectively. The difference between either two of them were statistically significant (P < 0.01). The MPO content and caspase-1 activity of rabbits in HFOV and HFOV + PS groups were obviously lower than those in control group (P < 0.01), and MPO content and caspase-1 activity of rabbits in HFOV + PS group were obviously lower than those in HFOV group (P < 0.05). In HFOV group and HFOV + PS group, the contents of TNF-alpha, IL-18 and their mRNA expression in lung tissue homogenates were obviously lower than those in control group (P < 0.01); while the contents of IL-10, IL-13 and their mRNA expression were obviously higher than those in control group (P < 0.01). Changes in these contents and expression in HFOV + PS group were more obvious than those in HFOV group (P < 0.05).

CONCLUSIONSHFOV can alleviate inflammatory response in rabbit lung tissue and pulmonary injury induced by inhalation injury, and the effect is more obvious when combined with PS.

Animals ; Burns, Inhalation ; complications ; therapy ; Disease Models, Animal ; High-Frequency Ventilation ; Inflammation ; Lung Injury ; etiology ; therapy ; Pulmonary Surfactants ; therapeutic use ; Rabbits